Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia Journal Article


Authors: Xiao, W.; Goldberg, A. D.; Famulare, C. A.; Devlin, S. M.; Nguyen, N. T.; Sim, S.; Kabel, C. C.; Patel, M. A.; McGovern, E. M.; Patel, A.; Schulman, J.; Dunbar, A. J.; Epstein-Peterson, Z. D.; Menghrajani, K. N.; Getta, B. M.; Cai, S. F.; Geyer, M. B.; Glass, J. L.; Taylor, J.; Viny, A. D.; Levine, R. L.; Zhang, Y.; Giralt, S. A.; Klimek, V.; Tallman, M. S.; Roshal, M.
Article Title: Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
Abstract: Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and difficult to standardize. Here we demonstrate that loss of plasmacytoid dendritic cell differentiation after 7+3 induction in AML is highly specific for measurable residual disease positivity (specificity 97.4%) in a uniformly treated patient cohort. Moreover, loss of plasmacytoid dendritic cell differentiation as determined by a blast-to-plasmacytoid dendritic cell ratio >10 was strongly associated with inferior overall and relapse-free survival (RFS) [Hazard ratio 2.79, 95% confidence interval (95%CI): 0.98-7.97; P=0.077) and 3.83 (95%CI: 1.51-9.74; P=0.007), respectively), which is similar in magnitude to measurable residual disease positivity. Importantly, measurable residual disease positive patients who reconstituted plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) showed a higher rate of measurable residual disease clearance at later pre-transplant time points compared to patients with loss of plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) (6 of 12, 50% vs 2 of 18, 11%; P=0.03). Furthermore pre-transplant plasmacytoid dendritic cell recovery was associated with superior outcome in measurable residual disease positive patients. Our study provides a novel, simple, broadly applicable, and quantitative multi-color flow cytometry approach to risk stratification in AML. Copyright© 2019 Ferrata Storti Foundation.
Journal Title: Haematologica
Volume: 104
Issue: 7
ISSN: 0390-6078
Publisher: Ferrata Storti Foundation  
Date Published: 2019-07-01
Start Page: 1378
End Page: 1387
Language: English
DOI: 10.3324/haematol.2018.203018
PUBMED: 30523054
PROVIDER: scopus
PMCID: PMC6601104
DOI/URL:
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
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MSK Authors
  1. Virginia Klimek
    132 Klimek
  2. Sergio Andres Giralt
    754 Giralt
  3. Martin Stuart Tallman
    568 Tallman
  4. Ross Levine
    617 Levine
  5. Sheng Feng Cai
    21 Cai
  6. Minal A Patel
    62 Patel
  7. Sean McCarthy Devlin
    442 Devlin
  8. Mikhail Roshal
    148 Roshal
  9. Aaron David Viny
    45 Viny
  10. Jacob Lowell Glass
    31 Glass
  11. Nghia Trong Nguyen
    4 Nguyen
  12. Mark Blaine Geyer
    47 Geyer
  13. Bartlomiej Marcin Getta
    27 Getta
  14. Justin   Taylor
    44 Taylor
  15. Yanming Zhang
    98 Zhang
  16. Andrew Jeffrey Dunbar
    22 Dunbar
  17. Wenbin Xiao
    51 Xiao
  18. Charlene Claire Kabel
    10 Kabel
  19. Akshar Patel
    12 Patel
  20. Sinnifer Sim
    1 Sim